Prospect of immunotherapy combined with anti-angiogenic agents in patients with advanced non-small cell lung cancer

In the latest years, some drugs have been approved by European Medicines Agency (EMA) and/or the US Food and Drug Administration (FDA) for the treatment of patients with advanced non-small cell lung cancer (NSCLC), particularly for the treatment of those who have no targeted gene mutations or who have progressed on previously targeted therapy or platinum-containing dual-agent chemotherapy. In general, these drugs fall into two categories: anti-angiogenic agents and immune checkpoint inhibitors (ICIs). Anti-angiogenic agents currently approved by the FDA and/or EMA for advanced NSCLC treatment include bevacizumab, nintedanib, and ramucirumab. Anlotinib has been approved in advanced NSCLC by Chinese Food and Drug Administration (CFDA). These anti-angiogenic agents can induce anti-angiogenesis by targeting vascular endothelial growth factor (VEGF)/VEGF2 or inhibiting multiple small molecules involved in angiogenic and proliferative pathways such as platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs). Although these drugs show significant therapeutic efficacy, most patients inevitably experience disease progression resulting in death. ICIs approved by the FDA and/or EMA for advanced NSCLC treatment include nivolumab, pembrolizumab, and atezolizumab. These ICIs can significantly improve efficacy compared with standard chemotherapy by targeting programmed cell death protein 1 (PD-1) receptor or PD-2 receptor with longer response duration and acceptable toxicity. However, the response rate of ICIs is suboptimal, and only a few patients ultimately benefit from immunotherapy. So current efforts have focused on exploring new potential combinatorial strategies with synergistic antitumor activity. Here, we summarized the theoretical basis, current clinical data, and potential future perspective of immunotherapy combined with anti-angiogenic agents for advanced NSCLC.